Antibiotics such as clarithromycin and erythromycin has been used in the treatment of common pediatric infections of the middle ear and upper respiratory tract, as well as certain forms of pneumonia that affects the elderly. However, such antibiotics are extremely bitter, and even when dissolved in trace quantities in a liquid dosage form are often perceived to be unpalatable. Administration of such antibiotics to children and the elderly poses a challenge as these patients experience difficulty in swallowing solid oral dosage forms. For these patients, antibiotics are typically provided in liquid forms, such as solutions, emulsions, and suspensions, which usually permit perceptible exposure of the antibiotic to the taste bud.
There is a need to mask the taste of such antibiotics in order to ensure patient compliance during therapy. Conventional taste masking techniques, such as the use of sweeteners, amino acids, and flavoring agents often are unsuccessful in masking the taste of highly bitter drugs and, consequently, other techniques need to be exploited for effectively masking the taste of these antibiotics.
One such technique involves the use of cation exchange resins, such as polysulfonic acid and polycarboxylic acid polymers, to adsorb amine drugs for taste masking and sustained release. However, this technique has limited applicability and is not capable of masking the taste of highly bitter drugs.
Coating of bitter drugs is another method which has been reported for taste masking. This technique alone may prove effective for moderately bitter drugs or in products where the coated particles are formulated as aqueous preparations before administration or are formulated in a non-aqueous medium. This technique has its limitations as coating of fine particles is usually technology intensive and coated granules are readily ruptured by chewing and compression.
Lipid-based microencapsulation is another technique used to taste mask the drugs. This technique requires highly sophisticated hot-melt granulation for producing fine particles, and may have adverse effects on heat sensitive molecules or restrict drug release adversely. U.S. Pat. No. 4,865,851 describes cefuroxime axetil in particulate form coated with an integral coating of lipid or a mixture of lipids.
U.S. Pat. No. 4,808,411 describes a taste-masked composition in the form of granules which contain clarithromycin and a carbomer acrylic acid polymer. The clarithromycin and carbomer are believed to be held together by both the ionic interactions between the amine group of clarithromycin and the carbonyl group of the carbomer and by the gel properties of the carbomer. This complex is further taste masked by coating.
U.S. Pat. No. 5,286,489 describes a porous drug-polymer matrix formed by admixing one or more bitter tasting active ingredient and a methyl methacrylic ester copolymer in at least a 1:1 by weight ratio of active ingredient to copolymer, effective to mask the taste of the drug. None of the examples described in U.S. Pat. No. 5,286,489 describe the effect of such polymers on the release of the drug from the matrix. While such a drug-polymer matrix may result in good taste-masking, the matrix may also retard the rate of drug release from the matrix to an extent which would be unacceptable for a conventional immediate-release formulation.
U.S. Pat. No. 5,633,006 describes a taste-masked composition containing a bitter pharmaceutical agent such as azithromycin, an alkaline earth oxide such as magnesium oxide, and a pharmaceutically acceptable carrier.
U.S. Pat. No. 6,565,877 describes a taste-masked composition containing a bitter tasting drug, such as clarithromycin, and a combination of two enteric polymers comprising a methacrylic acid copolymer and a phthalate polymer, wherein the ratio of methacrylic acid copolymer to phthalate polymer is between 1:9 or 9:1.
International Application WO 03/082248 describes a pharmaceutical composition containing erythromycin A or a derivative thereof, such as clarithromycin, and alginic agid.
International Application WO 03/082241 describes a pharmaceutical composition containing micronized clarithromycin. The clarithromycin has a particle size less than 35 microns.